Pilot trial of a novel two-step therapy protocol using nebulized tranexamic acid and recombinant factor VIIa in children with intractable diffuse alveolar hemorrhage

BACKGROUND AND OBJECTIVES: Diffuse alveolar hemorrhage (DAH) is a life threatening condition with very limited, often unsuccessful, therapeutic options. This study aimed at exploring the feasibility and efficacy of nebulized tranexamic acid TXA (n-TXA) and nebulized recombinant factor VIIa (n-rFVIIa) when used in a two-step therapy protocol in children with intractable DAH in a pediatric intensive care unit. METHODS: In a prospective trial, n-TXA (250 mg/dose for children < 25 kg and 500 mg/dose for children > 25 kg) was administered to 18 children (median age [interquartile range]; 24.0 months [11.3, 58.5]) with intractable DAH. N-rFVIIa (35 mu g/kg/dose for children < 25 kg, and 50 mu g/kg/dose for children > 25 kg) was added if no or minimal response was seen after 3 to 4 doses (18 to 24 hours) of n-TXA. RESULTS: DAH was stopped in 10 (55.6%) children with n-TXA alone within 24 hours of therapy. Documented concomitant respiratory infection showed a significant negative association with response to n-TXA in a step-wise regression analysis (OR= 0.06; 95% CI= 0.01-0.74). In the other 8 (44.4%) children, n-rFVIIa was added due to n-TXA failure. Six (75.0%) showed complete cessation of DAH, while two children failed to respond with the addition of n-rFVIIa (25.0%). None of the children who responded to therapy showed recurrence of DAH after therapy termination. No complications related to therapy were recorded. CONCLUSIONS: n-TXA and n-rFVIIa were effective and safe when used in a two-step-therapy protocol to control intractable DAH in pediatric patients in intensive care settings. This therapy modality warrants further exploration through larger multicenter clinical trials.